8号染色体上的新型阿尔茨海默病基因座。
New Alzheimer's disease locus on chromosome 8.
作者信息
Giedraitis V, Hedlund M, Skoglund L, Blom E, Ingvast S, Brundin R, Lannfelt L, Glaser A
机构信息
Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden .
出版信息
J Med Genet. 2006 Dec;43(12):931-5. doi: 10.1136/jmg.2006.043000. Epub 2006 Jul 6.
BACKGROUND
Family history is one of the most consistent risk factors for dementia. Therefore, analysis of families with a distinct inheritance pattern of disease can be a powerful approach for the identification of previously unknown disease genes.
OBJECTIVE
To map susceptibility regions for Alzheimer's disease.
METHODS
A complete genome scan with 369 microsatellite markers was carried out in 12 extended families collected in Sweden. Age at disease onset ranged from 53 to 78 years, but in 10 of the families there was at least one member with age at onset of < or =65 years. Mutations in known early-onset Alzheimer's disease susceptibility genes have been excluded. All people were genotyped for APOE, but no clear linkage with the epsilon4 allele was observed.
RESULTS
Although no common disease locus could be found in all families, in two families an extended haplotype was identified on chromosome 8q shared by all affected members. In one of the families, a non-parametric multimarker logarithm of the odds (LOD) score of 4.2 (p = 0.004) was obtained and analysis based on a dominant model showed a parametric LOD score of 2.4 for this region. All six affected members of this family shared a haplotype of 10 markers spanning about 40 cM. Three affected members in another family also shared a haplotype in the same region.
CONCLUSION
On the basis of our data, we propose the existence of a dominantly acting Alzheimer's disease susceptibility locus on chromosome 8.
背景
家族病史是痴呆症最一致的风险因素之一。因此，分析具有独特疾病遗传模式的家族可能是识别此前未知疾病基因的有力方法。
目的
绘制阿尔茨海默病的易感区域图谱。
方法
对在瑞典收集的12个大家庭进行了包含369个微卫星标记的全基因组扫描。疾病发病年龄在53岁至78岁之间，但在其中10个家庭中至少有一名成员发病年龄≤65岁。已知早发性阿尔茨海默病易感基因的突变已被排除。所有个体均进行了APOE基因分型，但未观察到与ε4等位基因的明确连锁关系。
结果
虽然在所有家庭中未发现共同的疾病位点，但在两个家庭中，所有患病成员在8号染色体上共享一个延伸单倍型。在其中一个家庭中，获得了非参数多标记优势对数（LOD）分数为4.2（p = 0.004），基于显性模型的分析显示该区域的参数LOD分数为2.4。这个家庭的所有6名患病成员共享一个包含10个标记、跨度约40 cM的单倍型。另一个家庭中的3名患病成员也在同一区域共享一个单倍型。
结论
根据我们的数据，我们提出8号染色体上存在一个显性作用的阿尔茨海默病易感基因座。
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